C4B and hand, foot and mouth disease: Our present and previous data indicated that C4b viruses had been circulating in mainland China for 5 years since 1998 (C4b was prevalent from 1998 to 2003 but has now disappeared from mainland China), which rarely caused severe disease and death in HFMD patients, and replaced by C4a viruses causing the nationwide outbreak with higher morbidity and mortality and caused many severe and fatal HFMD patients since 2007.